Association between serotonin 5-HT-2C receptor gene (HTR2C) polymorphisms and obesity- and mental health-related phenotypes in a large population-based cohort

OBJECTIVE: Studies have shown that common single-nucleotide polymorphisms (SNPs) in the serotonin 5-HT-2C receptor (HTR2C) are associated with antipsychotic agent-induced weight gain and the development of behavioural and psychological symptoms. We aimed to analyse whether variation in the HTR2C is associated with obesity- and mental health-related phenotypes in a large population-based cohort. METHOD: Six tagSNPs, which capture all common genetic variation in the HTR2C gene, were genotyped in 4978 men and women from the European Prospective Investigation into Cancer (EPIC)-Norfolk study, an ongoing prospective population-based cohort study in the United Kingdom. To confirm borderline significant associations, the -759C/T SNP (rs3813929) was genotyped in the remaining 16 003 individuals from the EPIC-Norfolk study. We assessed social and psychological circumstances using the Health and Life Experiences Questionnaire. Genmod models were used to test associations between the SNPs and the outcomes. Logistic regression was performed to test for association of SNPs with obesity- and mental health- related phenotypes. RESULTS: Of the six HTR2C SNPs, only the T allele of the -759C/T SNP showed borderline significant associations with higher body mass index (BMI) (0.23 kg m(-2); (95% confidence interval (CI): 0.01-0.44); P=0.051) and increased risk of lifetime major depressive disorder (MDD) (Odds ratio (OR): 1.13 (95% CI: 1.01-1.22), P=0.02). The associations between the -759C/T and BMI and lifetime MDD were independent. As associations only achieved borderline significance, we aimed to validate our findings on the -759C/T SNP in the full EPIC-Norfolk cohort (n=20 981). Although the association with BMI remained borderline significant (beta=0.20 kg m(-2); 95% CI: 0.04-0.44, P=0.09), that with lifetime MDD (OR: 1.01; 95% CI: 0.94-1.09, P=0.73) was not replicated. CONCLUSIONS: Our findings suggest that common HTR2C gene variants are unlikely to have a major role in obesity- and mental health-related traits in the general population.

Factors affecting hydrogen uptake by bacteria growing in the human large intestine

The human large intestine is a highly complex ecosystem that contains somewhere in the region of 400 different species of bacterial1.The vast majority of these bacteria are strict anaerobes and grow on a wide variety of substrates that have either escaped digestion in the small bowel or have been produced by the host2. In Western populations, between 10–60g of carbohydrate and 6–18g of proteinaceous material are potentially available for fermentation each day, producing a total bacterial mass of approximately 90g3.

Antidepressant treatment and emotional processing: can we dissociate the roles of serotonin and noradrenaline?

The ability to match individual patients to tailored treatments has the potential to greatly improve outcomes for individuals suffering from major depression. In particular, while the vast majority of antidepressant treatments affect either serotonin or noradrenaline or a combination of these two neurotransmitters, it is not known whether there are particular patients or symptom profiles which respond preferentially to the potentiation of serotonin over noradrenaline or vice versa. Experimental medicine models suggest that the primary mode of action of these treatments may be to remediate negative biases in emotional processing. Such models may provide a useful framework for interrogating the specific actions of antidepressants. Here, we therefore review evidence from studies examining the effects of drugs which potentiate serotonin, noradrenaline or a combination of both neurotransmitters on emotional processing. These results suggest that antidepressants targeting serotonin and noradrenaline may have some specific actions on emotion and reward processing which could be used to improve tailoring of treatment or to understand the effects of dual-reuptake inhibition. Specifically, serotonin may be particularly important in alleviating distress symptoms, while noradrenaline may be especially relevant to anhedonia. The data reviewed here also suggest that noradrenergic-based treatments may have earlier effects on emotional memory that those which affect serotonin.

Assessment of plant uptake models used in exposure assessment tools for soils contaminated with organic pollutants

The aim of this study was to evaluate and improve the accuracy of plant uptake models for neutral hydrophobic organic pollutants (1 < logKOW < 9, −8 < logKAW < 0) used in regulatory exposure assessment tools, using uncertainty and sensitivity analyses. The models considered were RAIDAR, EUSES, CSOIL, CLEA, and CalTOX. In this research, CSOIL demonstrated the best performance of all five exposure assessment tools for root uptake from polluted soil in comparison with observed data, but no model predicted shoot uptake well. Recalibration of the transpiration and volatilisation parameters improved the performance of CSOIL and CLEA. The dominant pathway for shoot uptake simulated differed according to the properties of the chemical under consideration; those with a higher air–water partition coefficient were transported into shoots via the soil-air-plant pathway, while chemicals with a lower octanol–water partition coefficient and air–water partition coefficient were transported via the root. The soil organic carbon content was a particularly sensitive parameter in each model and using a site specific value improved model performance.

Ocean heat uptake processes: a model intercomparison

We compare the quasi-equilibrium heat balances, as well as their responses to 4×CO2 perturbation, among three global climate models with the aim to identify and explain inter-model differences in ocean heat uptake (OHU) processes. We find that, in quasi-equilibrium, convective and mixed layer processes, as well as eddy-related processes, cause cooling of the subsurface ocean. The cooling is balanced by warming caused by advective and diapycnally diffusive processes. We also find that in the CO2-perturbed climates the largest contribution to OHU comes from changes in vertical mixing processes and the mean circulation, particularly in the extra-tropics, caused both by changes in wind forcing, and by changes in high-latitude buoyancy forcing. There is a substantial warming in the tropics, a significant part of which occurs because of changes in horizontal advection in extra-tropics. Diapycnal diffusion makes only a weak contribution to the OHU, mainly in the tropics, due to increased stratification. There are important qualitative differences in the contribution of eddy-induced advection and isopycnal diffusion to the OHU among the models. The former is related to the different values of the coefficients used in the corresponding scheme. The latter is related to the different tapering formulations of the isopycnal diffusion scheme. These differences affect the OHU in the deep ocean, which is substantial in two of the models, the dominant region of deep warming being the Southern Ocean. However, most of the OHU takes place above 2000 m, and the three models are quantitatively similar in their global OHU efficiency and its breakdown among processes and as a function of latitude.

The impact of salinity perturbations on the future uptake of heat by the Atlantic Ocean

Anthropogenic ocean heat uptake is a key factor in determining climate change and sea-level rise. There is considerable uncertainty in projections of freshwater forcing of the ocean, with the potential to influence ocean heat uptake. We investigatethis by adding either -0.1 Sv or +0.1 Sv freshwater to the Atlantic in global climate model simulations, simultaneously imposing an atmospheric CO2 increase. The resulting changes in the Atlantic meridional overturning circulation are roughly equal and opposite (±2Sv). The impact of the perturbation on ocean heat content is more complex, although it is relatively small (~5%) compared to the total anthropogenic heat uptake. Several competing processes either accelerate or retard warming at different depths. Whilst positive freshwater perturbations cause an overall heating of the Atlantic, negative perturbations produce insignificant net changes in heat content. The processes active in our model appear robust, although their net result is likely model- and experiment-dependent.

An isotope dilution model for partitioning phenylalanine and tyrosine uptake by the mammary gland of lactating dairy cows

An isotope dilution model for partitioning phenylalanine and tyrosine uptake by the mammary gland of the lactating dairy cow is constructed and solved in the steady state. The model contains four intracellular and four extracellular pools and conservation of mass principles are applied to generate the fundamental equations describing the behaviour of the system. The experimental measurements required for model solution are milk secretion and plasma flow rate across the gland in combination with phenylalanine and tyrosine concentrations and plateau isotopic enrichments in arterial and venous plasma and free and protein bound milk during a constant infusion of [1-(13)C]phenylalanine and [2,3,5,6-(2)H]tyrosine tracer. If assumptions are made, model solution enables determination of steady state flows for phenylalanine and tyrosine inflow to the gland, outflow from it and bypass, and flows representing the synthesis and degradation of constitutive protein and hydroxylation. The model is effective in providing information about the fates of phenylalanine and tyrosine in the mammary gland and could be used as part of a more complex system describing amino acid metabolism in the whole ruminant.

A process-based analysis of ocean heat uptake in an AOGCM with an eddy-permitting ocean component

About 90% of the anthropogenic increase in heat stored in the climate system is found the oceans. Therefore it is relevant to understand the details of ocean heat uptake. Here we present a detailed, process-based analysis of ocean heat uptake (OHU) processes in HiGEM1.2, an atmosphere-ocean general circulation model (AOGCM) with an eddy-permitting ocean component of 1/3 degree resolution. Similarly to various other models, HiGEM1.2 shows that the global heat budget is dominated by a downward advection of heat compensated by upward isopycnal diffusion. Only in the upper tropical ocean do we find the classical balance between downward diapycnal diffusion and upward advection of heat. The upward isopycnal diffusion of heat is located mostly in the Southern Ocean, which thus dominates the global heat budget. We compare the responses to a 4xCO2 forcing and an enhancement of the windstress forcing in the Southern Ocean. This highlights the importance of regional processes for the global ocean heat uptake. These are mainly surface fluxes and convection in the high latitudes, and advection in the Southern Ocean mid-latitudes. Changes in diffusion are less important. In line with the CMIP5 models, HiGEM1.2 shows a band of strong OHU in the mid-latitude Southern Ocean in the 4xCO2 run, which is mostly advective. By contrast, in the high-latitude Southern Ocean regions it is the suppression of convection that leads to OHU. In the enhanced windstress run, convection is strengthened at high Southern latitudes, leading to heat loss, while the magnitude of the OHU in the Southern mid-latitudes is very similar to the 4xCO2 results. Remarkably, there is only very small global OHU in the enhanced windstress run. The wind stress forcing just leads to a redistribution of heat. We relate the ocean changes at high southern latitudes to the effect of climate change on the Antarctic Circumpolar Current (ACC). It weakens in the 4xCO2 run and strengthens in the wind stress run. The weakening is due to a narrowing of the ACC, caused by an expansion of the Weddell Gyre, and a flattening of the isopycnals, which are explained by a combination of the wind stress forcing and increased precipitation.

Long term individual load forecast under different electrical vehicles uptake scenarios

More and more households are purchasing electric vehicles (EVs), and this will continue as we move towards a low carbon future. There are various projections as to the rate of EV uptake, but all predict an increase over the next ten years. Charging these EVs will produce one of the biggest loads on the low voltage network. To manage the network, we must not only take into account the number of EVs taken up, but where on the network they are charging, and at what time. To simulate the impact on the network from high, medium and low EV uptake (as outlined by the UK government), we present an agent-based model. We initialise the model to assign an EV to a household based on either random distribution or social influences - that is, a neighbour of an EV owner is more likely to also purchase an EV. Additionally, we examine the effect of peak behaviour on the network when charging is at day-time, night-time, or a mix of both. The model is implemented on a neighbourhood in south-east England using smart meter data (half hourly electricity readings) and real life charging patterns from an EV trial. Our results indicate that social influence can increase the peak demand on a local level (street or feeder), meaning that medium EV uptake can create higher peak demand than currently expected.

A traceable physical calibration of the vertical advection-diffusion equation for modelling ocean heat uptake

The classic vertical advection-diffusion (VAD) balance is a central concept in studying the ocean heat budget, in particular in simple climate models (SCMs). Here we present a new framework to calibrate the parameters of the VAD equation to the vertical ocean heat balance of two fully-coupled climate models that is traceable to the models’ circulation as well as to vertical mixing and diffusion processes. Based on temperature diagnostics, we derive an effective vertical velocity w∗ and turbulent diffusivity k∗ for each individual physical process. In steady-state, we find that the residual vertical velocity and diffusivity change sign in mid-depth, highlighting the different regional contributions of isopycnal and diapycnal diffusion in balancing the models’ residual advection and vertical mixing. We quantify the impacts of the time-evolution of the effective quantities under a transient 1%CO2 simulation and make the link to the parameters of currently employed SCMs.

Serotonin transporter [corrected] methylation and response to cognitive behaviour therapy in children with anxiety disorders

Anxiety disorders that are the most commonly occurring psychiatric disorders in childhood, are associated with a range of social and educational impairments and often continue into adulthood. Cognitive behaviour therapy (CBT) is an effective treatment option for the majority of cases, although up to 35-45% of children do not achieve remission. Recent research suggests that some genetic variants may be associated with a more beneficial response to psychological therapy. Epigenetic mechanisms such as DNA methylation work at the interface between genetic and environmental influences. Furthermore, epigenetic alterations at the serotonin transporter (SERT) promoter region have been associated with environmental influences such as stressful life experiences. In this study, we measured DNA methylation upstream of SERT in 116 children with an anxiety disorder, before and after receiving CBT. Change during treatment in percentage DNA methylation was significantly different in treatment responders vs nonresponders. This effect was driven by one CpG site in particular, at which responders increased in methylation, whereas nonresponders showed a decrease in DNA methylation. This is the first study to demonstrate differences in SERT methylation change in association with response to a purely psychological therapy. These findings confirm that biological changes occur alongside changes in symptomatology following a psychological therapy such as CBT.

Anticoagulant rodenticide uptake in resistant rat populations

The use of potent anticogulant rodenticide ‘resistance-breakers’ is avoided due to their higher toxicity and potential to be more hazardous in the environment [6]. However, in areas where practitioners seek to control resistant rodent infestations, their use may pose less of a risk than applications of ineffective baits. Compounds to which rodents are resistant to, do not provide effective control and create a long-term source of AR in the environment. The higher quantities of anticoagulant rodenticide used show that using ineffective compounds may extend both the period and severity of exposure to non-target animals to anticoagulant rodenticides. Conversely the effective use of resistance-breakers to control anticoagulant rodenticide-resistant rat populations results in lower environmental exposure of anticoagulant rodenticides for non-targets. Of course, the relative toxicity of the different anticoagulant rodenticides will also play an important part in overall risk assessments. However, this can be outweighed by the relative exposure to different anticoagulant rodenticides in such situations.

Uptake of agri-environmental schemes in the Less-Favoured Areas of Greece: The role of corruption and farmers' responses to the financial crisis

Vine-growing in the Less-Favoured Areas of Greece is facing multiple challenges that might lead to its abandonment. In an attempt to maintain rural populations, Rural Development Schemes have been created that offer the opportunity to rural households to maintain or expand their farming businesses including vine-growing. This paper stems from a study that used data from a cross-sectional survey of 204 farmers to investigate how farming systems and farmers’ perception of corruption, amongst other socio-economic factors, affected their decisions to continue vine-growing through participation in Rural Development Schemes, in three remote Less-Favoured Areas of Greece. The Theory of Planned Behaviour was used to frame the research problem with the assumption being that an individual’s intention to participate in a Scheme is based on their prior beliefs about it. Data from the survey were reduced and simplified by the use of non-linear principal component analysis. The ensuing variables were used in selectivity corrected ordered probit models to reveal farmers’ attitudes towards viticulture and rural development. It was found that economic factors, perceived corruption and farmers’ attitudes were significant determinants on whether to participate in the Schemes. The research findings highlight the important role of perceived corruption and the need for policies that facilitate farmers’ access to decision making centres.

Factors influencing European consumer uptake of personalised nutrition: results of a qualitative analysis

The aim of this research was to explore consumer perceptions of personalised nutrition and to compare these across three different levels of ‘‘medicalization’’: lifestyle assessment (no blood sampling); phenotypic assessment (blood sampling); genomic assessment (blood and buccal sampling). The protocol was developed from two pilot focus groups conducted in the UK. Two focus groups (one comprising only ‘‘older’’ individuals between 30 and 60 years old, the other of adults 18–65 yrs of age) were run in the UK, Spain, the Netherlands, Poland, Portugal, Ireland, Greece and Germany (N = 16). The analysis (guided using grounded theory) suggested that personalised nutrition was perceived in terms of benefit to health and fitness and that convenience was an important driver of uptake. Negative attitudes were associated with internet delivery but not with personalised nutrition per se. Barriers to uptake were linked to broader technological issues associated with data protection, trust in regulator and service providers. Services that required a fee were expected to be of better quality and more secure. An efficacious, transparent and trustworthy regulatory framework for personalised nutrition is required to alleviate consumer concern. In addition, developing trust in service providers is important if such services to be successful.

Nonlinearity of ocean heat uptake during warming and cooling in the FAMOUS climate model

Atmospheric CO2 concentration is expected to continue rising in the coming decades, but natural or artificial processes may eventually reduce it. We show that, in the FAMOUS atmosphere-ocean general circulation model, the reduction of ocean heat content as radiative forcing decreases is greater than would be expected from a linear model simulation of the response to the applied forcings. We relate this effect to the behavior of the Atlantic meridional overturning circulation (AMOC): the ocean cools more efficiently with a strong AMOC. The AMOC weakens as CO2 rises, then strengthens as CO2 declines, but temporarily overshoots its original strength. This nonlinearity comes mainly from the accumulated advection of salt into the North Atlantic, which gives the system a longer memory. This implies that changes observed in response to different CO2 scenarios or from different initial states, such as from past changes, may not be a reliable basis for making projections.